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Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science
Abstract
Background.—Comprehensive literature reviews of
historical perspectives and evidence supporting cannabis/
cannabinoids in the treatment of pain, including migraine
and headache, with associated neurobiological mechanisms
of pain modulation have been well described. Most of the
existing literature reports on the cannabinoids Δ9
-tetrahydrocannabinol (THC) and cannabidiol (CBD), or
cannabis in general. There are many cannabis strains that
vary widely in the composition of cannabinoids, terpenes,
flavonoids, and other compounds. These components work
synergistically to produce wide variations in benefits, side
effects, and strain characteristics. Knowledge of the individual
medicinal properties of the cannabinoids, terpenes, and
flavonoids is necessary to cross-breed strains to obtain
optimal standardized synergistic compositions. This will
enable targeting individual symptoms and/or diseases,
including migraine, headache, and pain.
Objective.—Review the medical literature for the use of
cannabis/cannabinoids in the treatment of migraine,
headache, facial pain, and other chronic pain syndromes, and
for supporting evidence of a potential role in combatting the
opioid epidemic. Review the medical literature involving
major and minor cannabinoids, primary and secondary
terpenes, and flavonoids that underlie the synergistic
entourage effects of cannabis. Summarize the individual
medicinal benefits of these substances, including analgesic
and anti-inflammatory properties.
Conclusion.—There is accumulating evidence for various
therapeutic benefits of cannabis/cannabinoids, especially in
the treatment of pain, which may also apply to the treatment
of migraine and headache. There is also supporting evidence
that cannabis may assist in opioid detoxification and weaning,
thus making it a potential weapon in battling the opioid
epidemic. Cannabis science is a rapidly evolving medical
sector and industry with increasingly regulated production
standards. Further research is anticipated to optimize
breeding of strain-specific synergistic ratios of cannabinoids,
terpenes, and other phytochemicals for predictable user
effects, characteristics, and improved symptom and diseasetargeted
therapies.
... Short-term studies suggest that it is well-accepted and has few negative side effects. In addition to the flavonoids found, the cannabinoids and terpenes in cannabis interact constantly to give the mentioned health advantages [69]. The terpenes obtained from hemp and their healing properties are mentioned in Table 2. Table 2. Biodynamic effects of the main terpenes found in Cannabis sativa L. [69]. ...
... In addition to the flavonoids found, the cannabinoids and terpenes in cannabis interact constantly to give the mentioned health advantages [69]. The terpenes obtained from hemp and their healing properties are mentioned in Table 2. Table 2. Biodynamic effects of the main terpenes found in Cannabis sativa L. [69]. ...
... Additionally, the mechanism through which CBD may have this diarrhea-inducing action is not well understood [65]. There are significant gaps in the literature regarding the possible long-term effects of CBD in healthy persons as well as the interaction of CBD with several molecular targets that are also involved in the control of neurophysiological processes; a significant information gap exists in research conducted on animals about the possible teratogenic and reprotoxic consequences of CBD exposure, particularly in females and in connection to lower dosages [69]. ...
Hemp is a high-value crop that originated in Central Asia and is a historic but emerging cultivated plant. It may be grown for fiber, food, paper making, textiles, and therapeutic reasons. In the 21st century, market interest in hemp and its products has notably increased because seed portions can be utilized in the agri-food business, the woody component of the stem can be used in green buildings, the outer layer of the stems can be used in the textile industry, and the extraction of bioactive components from roots can play a vital role in the pharmacological industries. Hemp has recently been demonstrated to be a viable alternative for economies built on synthetic materials by the food, pharmaceutical, textiles, paper, building, and energy industries, among others. As a result, the goal of this study is to assemble the significant advancements in hemp, as well as to identify research gaps and research direction opportunities. The hemp plant will be provided more encouragement to be grown and be used. Many applications of hemp may be pushed to the next level for both producing a green environment and profit. A strong vision and a well-defined plan will pave the path for the discovery of new technologies and concepts.
... In detail, it has been shown that these compounds can act on the same systems of opioid drugs through the activation of descendent inhibitory nociceptive pathways [18]. Several studies have reported that terpenes, such as myrcene, linalool, citronellol, and citronellal, exert analgesic effects through the modulation of the opioid system and the shutdown of the inflammatory response [19][20][21]. ...
... Cannabis sativa L. is gaining increasing relevance in scientific research due to the content of bioactive compounds, including terpenes [21,22]. Overall, the analgesic role of cannabinoids has been demonstrated in several pain conditions, both in animal models and in clinical studies through the modulation of the endogenous cannabinoid system in mammalian nociceptive pathways [23]. ...
... Here we focus on studying the mechanisms related to the modulation of orofacial pain by several bioactive compounds present in hemp, including terpenes. As previously discussed, Cannabis has up to 200 different terpenes, which are responsible for the varied aromas, flavors, and other characteristics of different strains [21]. Known as lipophilic molecules, they act at a wide range of sites, including neurotransmitter receptors, muscle, and neuronal ion channels, G-protein receptors, enzymes, cell membranes, and second messenger systems [83]. ...
The management of orofacial pain to alleviate the quality of life of affected patients is becoming increasingly challenging for scientific research and healthcare professionals. From this perspective, in addition to conventional therapies, new alternatives are being sought, increasingly looking at the use of both natural and synthetic products. Cannabis sativa L. represents an interesting source of bioactive compounds, including non-psychoactive cannabinoids, flavonoids, and terpenes, many of which are effective in improving pain intensity. Here, we aim to analyze the possible mechanisms of action of the bioactive natural and synthetic hemp-derived compounds responsible for the modulatory effects on pain-related pathways. The ability of these compounds to act on multiple mechanisms through a synergistic effect, reducing both the release of inflammatory mediators and regulating the response of the endocannabinoid system, makes them interesting agents for alternative formulations to be used in orofacial pain.
... Many studies suggest therapeutic synergies in cannabis, and it is often observed that the effects of the entire plant are greater than the effects of individual components [9, 12-14, 18, 19, 83, 84]. In addition to these studies, many consumers of cannabis attribute different physiological effects to different chemovars [9,11,12,19]. ...
... Although some chemovars might be inappropriate for some patients, with more than 700 chemovars available, the diversity of chemovars makes it likely that a chemovar with an appropriate balance of secondary metabolites could be found or bred for specific conditions and most patients [12,16,34]. ...
... Cannabis could potentially be used to treat multiple conditions simultaneously. Although in vivo studies and clinical trials are needed to determine if cannabis or cannabis secondary metabolites are suitable for treating S. aureus and MRSA infections, cannabis is already recognized for its analgesic properties [9,12,31]. Should cannabis prove suitable for S. aureus and MRSA treatment, it could potentially be used to treat both the infection and associated pain, possibly eliminating the need for a separate analgesic. Clinical trials could also be conducted to determine if cannabis could replace multiple drugs when treating S. aureus infection presenting with SEB-induced ARDS, as THC is a potent anti-inflammatory that halts the cytokine storm caused by the overactive immune response to SEB [45]. ...
Methicillin-resistant Staphylococcus aureus (MRSA) is a global health concern. Many antibiotics are no longer effective at treating MRSA, which causes an increase in adverse patient outcomes. This has led to calls for new antibiotics and treatment strategies to combat the spread of MRSA and multidrug resistance (MDR). The antimicrobial secondary metabolites found in plants are a promising source for new antibiotics and treatment strategies. Cannabis sativa L. is especially promising, as it produces dozens of antimicrobial secondary metabolites that are active against Staphylococcus aureus (S. aureus) and MRSA strains. In addition to its antimicrobial properties against S. aureus and MRSA, cannabis has many other desirable properties for potential antibiotics. Cannabis secondary metabolites are active against a wide range of microorganisms, are generally safe, target multiple bacterial processes and structures, have antimicrobial synergies, have a low potential for resistance development, can be produced inexpensively and combined with existing antibiotics to further reduce costs, and contain secondary metabolites capable of penetrating a variety of in vivo environments. These characteristics make cannabis a potential resource against MRSA and MDR bacteria.
... The therapeutic benefits of cannabis primarily come from cannabinoids derived from the plant, known as phytocannabinoids. Terpenes are also purported to contribute to the potential synergistic effects [55,56]. Cannabis is reported to contain approximately 120 phytocannabinoids and 150 terpenes; however, the pharmacology of only a few cannabinoids, such as tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabivarin (THCV), and terpenes such as pinene, beta-caryophyllene, myrcene, and humulene, have been studied [57][58][59]. ...
... from cannabinoids derived from the plant, known as phytocannabinoids. Terpenes are also purported to contribute to the potential synergistic effects [55,56]. Cannabis is reported to contain approximately 120 phytocannabinoids and 150 terpenes; however, the pharmacology of only a few cannabinoids, such as tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabivarin (THCV), and terpenes such as pinene, beta-caryophyllene, myrcene, and humulene, have been studied [57][58][59]. ...
Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have been utilized to alleviate pain, inflammation, anxiety, and gastrointestinal disorders like nausea, vomiting, diarrhoea, and inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures and religions. Despite multi-dimensional uses, the global prohibition of cannabis by the USA through the introduction of the Marijuana Tax Act in 1937 led to prejudice about the perceived risks of cannabis, overshadowing its medicinal potential. Nevertheless, the discovery of tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and the endocannabinoid system renewed scientific interest in understanding the role of cannabis in modulating different conditions, including gastrointestinal disorders. Preparations combining cannabidiol and THC have shown promise in mitigating gut symptoms through anti-inflammatory and motility-enhancing effects. This review revisits the ethnomedicinal use of cannabis in gastrointestinal diseases and emphasizes the need for further research to determine optimal dosages, formulations, and safety profiles of cannabis-based medicines. It also underscores the future potential of cannabinoid-based therapies by leveraging the role of the expanded endocannabinoid system, an endocannabinoidome, in the modulation of gastrointestinal ailments.
... Cannabis sativa, commonly known as cannabis, has been used for years for recreational and, more importantly, therapeutic or medicinal purposes [1]. The cannabis plant contains a variety of phytochemicals, including flavonoids, terpenoids, phytocannabinoids, alkaloids, glycoproteins, and phytosteroids [2] (Figure 1). The most well-known and studied phytochemicals in cannabis are the cannabinoids. ...
... The most well-known and studied phytochemicals in cannabis are the cannabinoids. ∆9-tetrahydrocannabinol (THC) is the primary psychoactive cannabinoid, produced mainly in the leaves and flower buds of the plant [2]. Besides THC, there are also non-psychoactive cannabinoids with several medicinal properties, such as cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), etc. along with other non-cannabinoid constituents [3]. ...
Historically, cannabis has been valued for its pain-relieving, anti-inflammatory, and calming properties. Ancient civilizations like the Egyptians, Greeks, and Chinese medicines recognized their therapeutic potential. The discovery of the endocannabinoid system, which interacts with cannabis phytoconstituents, has scientifically explained how cannabis affects the human immune system, including the central nervous system (CNS). This review explores the evolving world of cannabis-based treatments, spotlighting its diverse applications. By researching current research and clinical studies, we probe into how cannabinoids like Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) help to manage conditions ranging from chronic pain, persistent inflammation, cancer, inflammatory bowel disease, and neurological disorders to even viral diseases such as Human Immunodeficiency virus (HIV), SARS-CoV-2. and the emerging monkeypox. The long-term recreational use of cannabis can develop into cannabis use disorder (CUD), and therefore, understanding the factors contributing to the development and maintenance of cannabis addiction, including genetic predisposition, neurobiological mechanisms, and environmental influences, will be timely. Shedding light on the adverse impacts of CUD underscores the importance of early intervention, effective treatment approaches, and public health initiatives to address this complex issue in an evolving landscape of cannabis policies and perceptions.
... Sin embargo, algunos estudios han advertido que el proceso de permeación de la piel de los ingredientes cannábicos (ejemplo el CBD) está influenciado por la forma cosmética, el ingrediente "vehículo" (Casiraghi et al., 2020), y la calidad de la materia prima (Baron, 2018). Otros estudios, han informado sobre los efectos de irritación y aler-genicidad de ingredientes (p.ej. ...
... La base de datos sobre sustancias e ingredientes cosméticos de la Comisión Europea-CosIng registra 48 ingredientes derivados de extracto, tintura o resina de C. sativa, advirtiendo que, está prohibido el uso en cosméticos de 13 de estos ingredientes (European Commission, 2022). Actualmente, se comercializan tres tipos de extractos con fitocannabinoides: aceite de cannabis full espectro rico en CBD y BCP (β-Carophyllene); aceite no psicoactivo con alto contenido de CBD, CBDA y CBG; y, aceite psicoactivo que contiene THC y CBD (Baron, 2018). En estos extractos, las concentraciones de los compuestos cannábicos dependen de la variedad de cannabis, los métodos de extracción y la temperatura de almacenamiento (Wang et al., 2017). ...
A los ingredientes provenientes de la Cannabis sativa se les atribuyen numerosos beneficios para la piel, lo que ha dado lugar
al aumento vertiginoso de cosméticos que la incluyen en su formulación. El objetivo de este artículo es evaluar los cosméticos cannábicos de venta libre en Colombia, con especial interés en responder a la pregunta, si estos son recomendables
para su uso dermocosmético. Para cumplir con este objetivo se llevó a cabo una revisión sistemática de los ingredientes y las
características de 98 productos cosméticos para el cuidado de la piel con Notificación Sanitaria Obligatoria-NSO vigente en
el país. A grandes rasgos, está revisión arrojó que la mayoría (90%) de los cosméticos cannábicos disponibles en Colombia
son fabricados en el país. El 44% incluye en su formulación CBD, el 35% utiliza extractos de semilla de cannabis, mientras
que el 11% combina estos dos ingredientes. El análisis de los ingredientes reveló varias debilidades en la composición de
estos productos que limitan su uso dermocosmético. En algunos otros casos, se observaron ingredientes que incluso podrían
representar riesgos para la salud de la piel. Los hallazgos de esta revisión llevan a concluir que los cosméticos cannábicos
comercializados en el país no cuentan con estudios de aceptabilidad y eficacia que respalden su uso dermocosmético, ni
tampoco con pruebas que justifiquen muchas de las acciones cosméticas que indican en sus etiquetas. Dado la gran cantidad
de opciones de cosméticos cannábicos de venta libre, es recomendable que los consumidores verifiquen si estos cosméticos
cuentan con evidencia clínica que justifique su uso dermocosmético.
... Tar is common for both, but there is a lack of nicotine in cannabis products and a lack of tetrahydrocannabinol (THC), while there is a trace amount of THC-like constituents (cannabinoids) in tobacco products (34). This means that marijuana is carcinogenic, as it consists of compounds named polycyclic aromatic hydrocarbons such as benzo[a]pyrene, a key factor that induces cancer in human lungs (35). Lack of filters in marijuana cigarettes brought a two-fold more inhaling tar than that of tobacco, per unit weight in addition to the same profile of smoke (36). ...
... Marijuana is carcinogenic, with its compounds named polycyclic aromatic hydrocarbons such as benzo[a]pyrene being a key factor for the progress of cancer in the human lungs (35). Histological tests of biopsied bronchial samples from marijuana users demonstrated a predisposition to premalignant changes (53). ...
Cannabis presents itself as another challenge of the last decade. Better and better deciphered through in-depth studies, this drug remains a source of scientific debates. Legalized in some states, it competes with tobacco regarding the effects generating respiratory symptoms, chronic bronchitis, bronchial cancer, respiratory infections, etc. In this article we will review the pharmacology, epidemiology, clinical and prevention aspects and try to demonstrate which of these are the most effective means of prevention. This review proves once again that this drug has many hidden dangers.
... They are the bioproduct of primary as well secondary plant metabolism which may facilitate diverse eco-interactive functions, being as plant self-defense system reproduction, communication, climatic acclimation, and others. Terpenes and isoprenoids found in higher plants can be used in a wide broad-spectrum application such as pharmaceutical drugs, cosmetics, food and beverages, confectionaries, biofuel, and rubber derivatives (Baron 2018;Guimarães et al. 2014;Tetali 2019). They described a broad range of the biological properties of terpenes and terpenoids, including pharmacological activity such as anticancer, antimicrobial, antifungal, antiviral, antihyperglycemic, analgesic, anti-inflammatory, and antiparasitic (Paduch et al. 2007). ...
... Several terpenes fill the requirements as potential, fill the requirement as potential pharmacological treatments to neurodegenerative diseases, mainly due to their properties, such as lipophilicity, and have widely variable sites of action including neurotransmitter receptors, muscle and neuronal ion channels, G protein-coupled receptors, enzymes, cell membranes, and second messenger systems (Baron 2018). Considering the ALS pathophysiologic features, such as neuroinflammation, oxidative stress, and glutamate excitotoxicity (Liu and Wang 2017;Zarei et al. 2015;Trias et al. 2018), terpenoids are good candidates for treatment and more studies are necessary in ALS study models. ...
Amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by progressive motor neuron degeneration. Conventional therapies for ALS are based on treatment of symptoms, and the disease remains incurable. Molecular mechanisms are unclear, but studies have been pointing to involvement of glia, neuroinflammation, oxidative stress, and glutamate excitotoxicity as a key factor. Nowadays, we have few treatments for this disease that only delays death, but also does not stop the neurodegenerative process. These treatments are based on glutamate blockage (riluzole), tyrosine kinase inhibition (masitinib), and antioxidant activity (edaravone). In the past few years, plant-derived compounds have been studied for neurodegenerative disorder therapies based on neuroprotection and glial cell response. In this review, we describe mechanisms of action of natural compounds associated with neuroprotective effects, and the possibilities for new therapeutic strategies in ALS.
... This retrospective medical record review describes the population characteristics of patients using medicinal cannabis at a clinic in Sydney, Australia and provides data on the effectiveness and safety of medicinal cannabis treatment on patient conditions and indications. In our study, the mean age of patients was higher than in international studies (40-50 years) [14][15][16][17][18][19]. In Australia, patients must have trialed mainstream therapies before their medicinal cannabis application can be approved [4]. ...
... Literature shows that therapeutic doses of ∆-9-THC (5-20 mg) tend to be smaller than CBD (50-1500 mg) [4] and our study supports this finding. This is expected as CBD is non-psychoactive and may circumvent the side effects of ∆-9-THC [17]. Our study showed that higher doses of ∆-9-THC were used which may indicate that people with non-cancer conditions/indications may be able to tolerate higher doses compared to people with cancer, and this needs to be ascertained in clinical use [19]. ...
Research describing patients using medicinal cannabis and its effectiveness is lacking. We aimed to describe adults with non-cancer diagnoses who are prescribed medicinal cannabis via a retrospective medical record review and assess its effectiveness and safety. From 157 Australian records, most were female (63.7%; mean age 63.0 years). Most patients had neurological (58.0%) or musculoskeletal (24.8%) conditions. Medicinal cannabis was perceived beneficial by 53.5% of patients. Mixed-effects modelling and post hoc multiple comparisons analysis showed significant changes overtime for pain, bowel problems, fatigue, difficulty sleeping, mood, quality of life (all p < 0.0001), breathing problems (p = 0.0035), and appetite (p = 0.0465) Symptom Assessment Scale scores. For the conditions, neuropathic pain/peripheral neuropathy had the highest rate of perceived benefit (66.6%), followed by Parkinson’s disease (60.9%), multiple sclerosis (60.0%), migraine (43.8%), chronic pain syndrome (42.1%), and spondylosis (40.0%). For the indications, medicinal cannabis had the greatest perceived effect on sleep (80.0%), followed by pain (51.5%), and muscle spasm (50%). Oral oil preparations of balanced delta-9-tetrahydrocannabinol/cannabidiol (average post-titration dose of 16.9 mg and 34.8 mg per day, respectively) were mainly prescribed. Somnolence was the most frequently reported side effect (21%). This study supports medicinal cannabis’ potential to safely treat non-cancer chronic conditions and indications.
... CBD is a very important and well-known molecule because of its antioxidant, antiinflammatory, and antibiotic activity, as well as its anxiolytic and neuroprotective properties [5,6]. The extraction method chosen to extract CBD is based on the raw material source and the desired grade of selectivity. ...
In recent years, the increasing demand for alternative foods has shifted research toward new sources enriched with nutraceutical molecules. It is well known that many diseases are caused by oxidative stress; thus, the supplementation of antioxidants has been proposed to reduce it. Cannabis sativa L. is an interesting species that could provide an alternative source of antioxidants. This work aimed to investigate the possibility of optimizing the yield of cannabidiol (CBD) and recovering it from residual biomass (stalks), valorizing the residual biomass, and using this for protein bar preparation. Different extraction methods were used, and High-Pressure Liquid Chromatography (HPLC) analysis was used to analyze the extracts. Antioxidant power was investigated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. The best results in terms of CBD yield were obtained via dynamic maceration after decarboxylation with a quantity of 26.7 ± 2 mgCBD/graw material from inflorescences. The extract also shows good antioxidant power with an IC50 value of 38.1 ± 1.1 µg/mL measured using the DPPH assay. The CBD extract was added to the hemp oil to obtain dough for protein bars. The doughs were studied by taking rheological and technological measurements, and it was found that the protein bars could provide an excellent means for the consumption of products enriched with antioxidants because their CBD anti-inflammatory activity is preserved after cooking.
... CBD is a very important and well-known molecule because of its antioxidant, anti-inflammatory and antibiotic activity, anxiolytic and neuroprotective properties [5,6]. The extraction method chosen to extract CBD is based on the raw material source and the desired grade of selectivity. ...
(1) Background: In recent years, the increasing demand for alternative food shifted research toward new types of food sources. It is well known that many diseases are caused by oxidative stress, then supplementation of antioxidants can be proposed to reduce it. Cannabis Sativa (CS) is an interesting alternative source of antioxidant species. The use of CS for the extraction of these molecules could be optimized to maximize the antioxidant yield extracts. (2) Methods: This work aimed to investigate extraction methods of CBD oil from CS inflorescences and stalks to obtain antioxidant-enriched compounds for use in food by mixing with a carrier oil like hemp seed oil. Soxhlet (SE), dynamic maceration (DME) and supercritical fluid (SFE) extraction techniques were performed, using CS inflorescences and stalks; by High-Pressure Liquid Chromatography (HPLC) analysis the antioxidants were individuated and quantified; moreover, the antioxidant power was investigated by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays and finally doughs enriched with hemp oil were studied by rheological measurements (3) Results: The best results in terms of CBD yield were obtained by dynamic maceration from only flowers and it also shows a good antioxidant power. (4) Conclusions: Formulation of protein bars with hemp oil enriched in CBD could be an excellent means for the consumption of products enriched with antioxidants because it preserves the CBD anti-inflammatory activity.
... Fibromialgia, dolor crónico(Russo, 2019), Párkinson, alzhéimer, TBI (Traumatic brain injuries), migrañas(Baron, 2018), esclerosis lateral amiotrófica (ALS)(Urbi B, Broadley S, Bedlack R, et al, 2019), tumores(Likar and Nahler 2017), insomnio(Zhand and Milin, 2018), tourette, esclerosis múltiple, asperger (Crippa et al., 2010), enfermedad de Crohn y enfermedades intestinales(Naftali et al., 2011), anorexia y cáncer(Abrams, 2016), acné, dermatitis alérgica de contacto, dermatitis asteatótica, dermatitis atópica, hidradenitis supurativa, sarcoma de Kaposi, prurito, psoriasis, cáncer de piel y las manifestaciones cutáneas de esclerosis sistémica(Eagleston et al., 2018), artritis(Lowin y Straub, 2015). 5 Extracciones que se realizan a partir de las flores de la planta como: resina, tinturas, aceites, cremas, etc. ...
Since the enactment of Law 27,350 in 2017, the Argentine State has recognized the medicinal properties of the marijuana plant. However, to the understanding of many users and activists, the first regulation of the law resulted in a restrictive norm that hinders access, as it does not provide for self-cultivation. In other words, these practices were penalized by Argentina's drug control legislation - Law 23.737 - which allows security forces to continue raiding and arresting those who use
and grow cannabis.
This article is part of my research for my master's thesis in sociology. From a historical and relational perspective, it will address the emergence of the cannabis movement in Bahia Blanca town. Through ethnography, in-depth interviews, participant observation, data and documents from the field, we explore and describe the strategies and practices that users and growers of therapeutic/medicinal cannabis implemented to protect crops, prevent break-ins and robberies in Bahia Blanca, Buenos Aires,
Argentina, during 2015-2019.
... It is recommended for treating pain (including chronic and cancer-related), autoimmune diseases, mental illnesses, and others due to its naturalness [34][35][36]. Cannabis oil has no addictive or intoxicating effects, so many people can successfully supplement it [37]. CBD has a complex legal status that varies from country to country and region to region. ...
... Following this logic, since it is possible to obtain improvement of symptoms with CBD for patient safety, it does not make sense to start with products with a higher amount of THC, leaving this phytocannabinoid as a second option, i.e., in cases where CBD does not help [45][46][47][50][51][52][53][54] . It is increasingly becoming undisputed, despite the difficulties of scientific documentation within traditional metrics, the therapeutic potential of cannabis and its derivatives in controlling pain in patients who respond satisfactorily to one or more of its actives, being especially useful for those individuals who have obtained frustrating responses with conventional treatments [55][56][57][58][59][60][61][62] . ...
BACKGROUND AND OBJECTIVES
The individualization of treatment has been recognized as essential in medical practice, especially due to the demand for different therapeutic approaches for similar situations. However, the complex and variable nature of the phytocannabinoids present in the cannabis plant presents challenges for the application of traditional models for testing the efficacy and safety of new drugs. The objective of the present study was to highlight the particularities of cannabis, including genetic variety, cultivation and production, which make it difficult to comply with traditional drug registration protocols, and the importance of individualizing treatment in the use of cannabis for the control of pain.
CONTENTS
Traditional models for testing the efficacy and safety of new drugs are based on a rigid methodology, divided into development and post-market phases. However, the complexity of the cannabis plant, with hundreds of actives that can vary according to the genetic variety, cultivation and production process, makes the application of these models difficult. In addition, international rules do not allow the registration of patents on cannabis products, due to the consideration that they are natural products and the extraction methods are already used in the industry for other plant actives. The individualization of treatment is fundamental in the use of cannabis for pain control, given the complexity of the plant and the limitations of traditional models of testing and drug registration.
CONCLUSION
The particularities of cannabis, such as genetic variability and the impossibility of registering patents, make compliance with current protocols difficult. However, the individualization of treatment allows adapting therapies to the needs of each patient, considering effectiveness and tolerance of side effects. Therefore, there is a need to rethink research and registry models to allow for a more flexible and personalized approach in the field of cannabis medicines.
Keywords:
Cannabinoids receptors; Cannabis; Evidence-based pharmaceutical practice; History; Medical marijuana; Pain
... Products high in CBD versus THC lack the intoxicating/psychotropic effects of products that are higher in the latter compound, and CBD does not exhibit effects suggestive of abuse or dependence potential (WHO & Expert Committee on Drug Dependence, 2017). C. sativa plant extracts also generally include various non-cannabinoid constituents such as terpenes and flavonoids (Baron, 2018;ElSohly et al., 2017;Elsohly & Slade, 2005;Radwan et al., 2008). ...
Currently, there is much interest in the sales and study of consumable Cannabis sativa L. products that contain relatively high levels of cannabidiol (CBD) and low levels of Δ-9-tetrahydrocannabinol. While there are published safety evaluations for extracts containing low concentrations of CBD, toxicological assessments for those with higher concentrations are still scant in the public domain. In this paper, genotoxicity tests and a 90-day repeated-dose toxicity study of an ethanolic extract of C. sativa containing ~85% CBD were performed following relevant OECD guidelines. No increased gene mutations were observed in a bacterial reverse mutation assay compared to controls up to the maximum recommended concentration of the guideline. An in vitro chromosomal aberration assay showed no positive findings in the short-term (3 h) treatment assays. Long-term treatment (20 h) showed an increased number of cells containing aberrations at the highest dose of 2 μg/mL, which was outside of historical control levels, but not statistically significantly different from the controls. An in vivo micronucleus study showed no genotoxic potential of the test item in mice. A 90-day repeated-dose gavage study using 0, 75, 125, and 175 mg/kg bw/day showed several slight findings that were considered likely to be related to an adaptive response to consumption of the extract by the animals but were not considered toxicologically relevant. These included increases in liver and adrenal weights compared to controls. The NOAEL was determined as 175 mg/kg bw/day, the highest dose tested (equivalent to approximately 150 mg/kg bw/day of CBD).
... The main particulate constituent of the tobacco and cannabis abuse i.e., tar is common to both the substances while the presence of Marinol and other analogous structural compounds is present only in cannabis, when an analysis is carried on the comparative scale (Sharma, et al., 2012). The nicotine present in tar of tobacco is unique to it while at the same time cannabis lacks it, but, at the same time it cannot be argued that marijuana is not carcinogenic due to lack of nicotine, as the presence of chemical constituents like benzo[a]pyrene, which acts as a connecting link for the pulmonary oncogenesis (Do, et al., 2018). The difference in puffing of cigarettes laden with tobacco which contain a filter which reduces the tar content, while at the same time marijuana cigarettes does not contain any filter which increases the risk of tar content two-fold (Aldington, et al., 2008). ...
Cannabis sativa, popularly known as "marijuana," poses a problem since it may have both beneficial and harmful effects. Cannabis has long been used for medicinal and recreational purposes, which demonstrates its value as a plant. Instead of this, enough evidence suggests that abusing this wonder herb can have negative effects on a number of organs and organ systems, such as the pulmonary system, the body's defense system, the cardiovascular system, etc. Additionally, it may affect both male and female potency and may also have clastogenic effects. Yet, it cannot be ruled out that there are some benefits to using marijuana responsibly, since it has been shown to be a miraculous treatment for atrophy, acute pain, a loss of muscular tone, motion sickness, and insomnia. This chapter will attempt to provide a thorough understanding of the various health effects of the herb and its extracted active bioactive ingredients.
... Different studies in models of chronic pain demonstrate promising results using cannabidiol (CBD) treatments [23][24][25][26]. CBD is a phytocannabinoid and an exogenous endocannabinoid system modulator [27][28][29]. ...
Chronic neuropathic pain (CNP) is a vast world health problem often associated with the somatosensory domain. This conceptualization is problematic because, unlike most other sensations that are usually affectively neutral and may present emotional, affective, and cognitive impairments. Neuronal circuits that modulate pain can increase or decrease painful sensitivity based on several factors, including context and expectation. The objective of this study was to evaluate whether subchronic treatment with Cannabidiol (CBD; 0.3, 3, and 10mg/kg intraperitoneal route - i.p., once a day for 3 days) could promote pain-conditioned reversal, in the conditioned place preference (CPP) test, in male Wistar rats submitted to chronic constriction injury (CCI) of the sciatic nerve. Then, we evaluated the expression of astrocytes and microglia in animals treated with CBD through the immunofluorescence technique. Our results demonstrated that CBD promoted the reversal of CPP at 3 and 10mg/kg. In CCI animals, CBD was able to attenuate the increase in neuronal hyperactivity, measured by FosB protein expression, in the regions of the corticolimbic circuit: anterior cingulate cortex (ACC), complex basolateral amygdala (BLA), granular layer of the dentate gyrus (GrDG), and dorsal hippocampus (DH) - adjacent to subiculum (CA1). CBD also prevented the increased expression of GFAP and IBA-1 in CCI animals. We concluded that CBD effects on CNP are linked to the modulation of the aversive component of pain. These effects decrease chronic neuronal activation and inflammatory markers in regions of the corticolimbic circuit.
... These chemovars are analogous to phytochemical factories producing terpenes and cannabinoids, many with welldocumented medicinal properties. [15] This literature review begins by examining the literature, providing a psychosocial overview of posttraumatic stress disorder and the historically controversial and noncontroversial nature of the biologically derived molecules that have demonstrated efficacy in treating PTSD symptoms. Electronic databases of pharmacology and psychology and library journals, including Medline and other EBSCOhost Databases, were searched to examine theoretical frameworks related to phytochemicals and their potential usefulness in treating posttraumatic stress disorder, focusing on molecules inherent in chemovars of Cannabis sativa. ...
This literature review examines theoretical frameworks related to applying the principles of biomolecular psychology and psychoneuroimmunology to devise a nutraceutical protocol utilizing phytochemicals for the treatment of posttraumatic stress disorder with a particular focus on modulating the endocannabinoid system through the utilization of molecules inherent in chemovars of Cannabis sativa. It provides a psychosocial overview of posttraumatic stress disorder and the historically controversial and noncontroversial nature of the biologically derived molecules that have demonstrated efficacy in addressing the effects major stressors have on the biomolecular mechanisms that cause mood disorders that manifest themselves as symptoms of PTSD.
... In the flowers of pine, elderberry, eucalyptus, lime, in pine needles, sage, juniper, the terpene alpha-pinene was detected. It has anti-inflammatory, analgesic, antifungal, antiviral and antioxidant properties and is able to relax smooth muscles, making it a valuable remedy for asthma and inflammation of the respiratory tract (Karthikeyan, et al. [21][22][23][24]). Alpha-pinene facilitates respiration by dilating the airways (Adamski, et al. [25]). ...
... The two most abundant cannabinoids are Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) (Booth and Bohlmann 2019) and most commercial cannabis varieties are defined by their THC/CBD ratio. Cannabinoids modulate a variety of physiological processes such as neurocognition, appetite, pain, and immunity (Baron 2018;Costiniuk and Jenabian 2019;Nader and Sanchez 2018). THC is responsible for the psychoactive effects of cannabis whereas both THC and CBD are thought to have antiinflammatory properties. ...
Cannabis contains cannabinoids including Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC causes the psychoactive effects of cannabis, and both THC and CBD are thought to be anti-inflammatory. Cannabis is typically consumed by inhaling smoke that contains thousands of combustion products that may damage the lungs. However, the relationship between cannabis smoke exposure and alterations in respiratory health is poorly defined. To address this gap in knowledge, we first developed a mouse model of cannabis smoke exposure using a nose-only rodent inhalation exposure system. We then tested the acute effects of two dried cannabis products that differ substantially in their THC–CBD ratio: Indica-THC dominant (I-THC; 16–22% THC) and Sativa-CBD dominant (S-CBD; 13–19% CBD). We demonstrate that this smoke exposure regime not only delivers physiologically relevant levels of THC to the bloodstream, but that acute inhalation of cannabis smoke modulates the pulmonary immune response. Cannabis smoke decreased the percentage of lung alveolar macrophages but increased lung interstitial macrophages (IMs). There was also a decrease in lung dendritic cells as well as Ly6Cintermediate and Ly6Clow monocytes, but an increase in lung neutrophils and CD8⁺ T cells. These immune cell changes were paralleled with changes in several immune mediators. These immunological modifications were more pronounced when mice were exposed to S-CBD compared to the I-THC variety. Thus, we show that acute cannabis smoke differentially affects lung immunity based on the THC:CBD ratio, thereby providing a foundation to further explore the effect of chronic cannabis smoke exposures on pulmonary health.
... The main particulate constituent of the tobacco and cannabis abuse i.e., tar is common to both the substances while the presence of Marinol and other analogous structural compounds is present only in cannabis, when an analysis is carried on the comparative scale (Sharma, et al., 2012). The nicotine present in tar of tobacco is unique to it while at the same time cannabis lacks it, but, at the same time it cannot be argued that marijuana is not carcinogenic due to lack of nicotine, as the presence of chemical constituents like benzo[a]pyrene, which acts as a connecting link for the pulmonary oncogenesis (Do, et al., 2018). The difference in puffing of cigarettes laden with tobacco which contain a filter which reduces the tar content, while at the same time marijuana cigarettes does not contain any filter which increases the risk of tar content two-fold (Aldington, et al., 2008). ...
... Several studies have attempted to find a correlation between the terpene profiles of various chemovars and their impact on particular indications, e.g., anxiety [20,21] and pain [22]. Also related is the "sativa" vs. "indica" effect, mainly attributed to the chemovar/ product fit for energic activity vs. relaxation/sedation [23][24][25]. ...
The cannabis plant exerts its pharmaceutical activity primarily by the binding of cannabinoids to two G protein-coupled cannabinoid receptors, CB1 and CB2. The role that cannabis terpenes play in this activation has been considered and debated repeatedly, based on only limited experimental results. In the current study we used a controlled in-vitro heterologous expression system to quantify the activation of CB1 receptors by sixteen cannabis terpenes individually, by tetrahydrocannabinol (THC) alone and by THC-terpenes mixtures. The results demonstrate that all terpenes, when tested individually, activate CB1 receptors, at about 10-50% of the activation by THC alone. The combination of some of these terpenes with THC significantly increases the activity of the CB1 receptor, compared to THC alone. In some cases, several fold. Importantly, this amplification is evident at terpene to THC ratios similar to those in the cannabis plant, which reflect very low terpene concentrations. For some terpenes, the activation obtained by THC- terpene mixtures is notably greater than the sum of the activations by the individual components, suggesting a synergistic effect. Our results strongly support a modulatory effect of some of the terpenes on the interaction between THC and the CB1 receptor. As the most effective terpenes are not necessarily the most abundant ones in the cannabis plant, reaching "whole plant" or "full spectrum" composition is not necessarily an advantage. For enhanced therapeutic effects, desired compositions are attainable by enriching extracts with selected terpenes. These compositions adjust the treatment for various desired medicinal and personal needs.
... Su producto más valioso es una resina rica en terpenos y cannabinoides. Estos exhiben diversas propiedades psicoactivas y medicinales (Barón 2018), lo que ha generado un interés creciente en su producción comercial. En esta producción de cannabis con fines farmacéuticos, cuyas estrategias de manejo integrado de plagas restringen la aplicación de productos de síntesis química, la entomofauna presente se convierte en un componente fundamental del funcionamiento del sistema productivo (Taylor y Birkett 2020). ...
En la producción comercial de cannabis medicinal, donde se restringe la aplicación de productos de síntesis química, la entomofauna asociada es un componente fundamental del funcionamiento del sistema productivo. Su caracterización contribuye a la generación de estrategias encaminadas al mejoramiento de la producción. Preservar estos especímenes identificados y curados, constituye un archivo histórico natural de múltiple utilidad. El objetivo de este trabajo fue recolectar, determinar y preservar especímenes de artrópodos asociados al sistema productivo de cannabis medicinal. Se recorrieron las áreas de propagación, producción, investigación y postcosecha de un cultivo bajo invernadero. Los métodos de captura utilizados fueron trampas de luz, pases con red entomológica, aspirador entomológico, trampas de caída perimetrales y captura manual de especímenes que se estuvieran alimentando de los tejidos vegetales de las plantas. Los estados larvales se criaron hasta el estado adulto para lograr su identificación. Se obtuvieron 240 especímenes pertenecientes a 8 órdenes, 36 familias y 73 especies de insectos. El mayor porcentaje correspondió a los órdenes Coleoptera e Hymenoptera. En Coleoptera, se determinaron especies pertenecientes a las familias Melolonthidae, Carabidae y Silphidae, entre otros. Adicionalmente, algunas familias de Hymenoptera como Braconidae, Ichneumonidae y Formicidae. Las especies son reportadas de acuerdo con sus roles alimenticios y/o funcionales como fitófagos, polinizadores, detritívoros, necrófagos, coprófagos, micófagos, antófagos, parasitoides, predadores e hiperparásitoides. Se reconocieron 6 grupos de insectos nocivos para el cultivo: salta hojas, ácaros, trips, áfidos de hoja y raíz, mosca del mantillo y lepidópteros defoliadores. Este trabajo constituye un avance significativo en la investigación relacionada con la entomofauna asociada al sistema productivo de Cannabis sativa en Antioquia, Colombia.
... Su producto más valioso es una resina rica en terpenos y cannabinoides. Estos exhiben diversas propiedades psicoactivas y medicinales (Barón 2018), lo que ha generado un interés creciente en su producción comercial. En esta producción de cannabis con fines farmacéuticos, cuyas estrategias de manejo integrado de plagas restringen la aplicación de productos de síntesis química, la entomofauna presente se convierte en un componente fundamental del funcionamiento del sistema productivo (Taylor y Birkett 2020). ...
... Cannabis can be grown both indoors and outdoors and is dioecious (i.e., separate male and female plants). Cannabis is the third most prevalent psychoactive substance consumed after alcohol and tobacco [3][4][5][6]. Cannabis is also the most commonly-used illicit substance, with approximately 150 million users worldwide [7]. The psychoactive abilities of cannabis are due to the presence of the cannabinoid Δ 9 -tetrahydrocannabinol (Δ 9 -THC), but there are more than 100 other cannabinoids that could have alternative pharmacological properties. ...
The lungs, in addition to participating in gas exchange, represent the first line of defense against inhaled pathogens and respiratory toxicants. Cells lining the airways and alveoli include epithelial cells and alveolar macrophages, the latter being resident innate immune cells important in surfactant recycling, protection against bacterial invasion and modulation of lung immune homeostasis. Environmental exposure to toxicants found in cigarette smoke, air pollution and cannabis can alter the number and function of immune cells in the lungs. Cannabis (marijuana) is a plant-derived product that is typically inhaled in the form of smoke from a joint. However, alternative delivery methods such as vaping, which heats the plant without combustion, are becoming more common. Cannabis use has increased in recent years, coinciding with more countries legalizing cannabis for both recreational and medicinal purposes. Cannabis may have numerous health benefits owing to the presence of cannabinoids that dampen immune function and therefore tame inflammation that is associated with chronic diseases such as arthritis. The health effects that could come with cannabis use remain poorly understood, particularly inhaled cannabis products that may directly impact the pulmonary immune system. Herein, we first describe the bioactive phytochemicals present in cannabis, with an emphasis on cannabinoids and their ability to interact with the endocannabinoid system. We also review the current state-of-knowledge as to how inhaled cannabis/cannabinoids can shape immune response in the lungs and discuss the potential consequences of altered pulmonary immunity. Overall, more research is needed to understand how cannabis inhalation shapes the pulmonary immune response to balance physiological and beneficial responses with potential deleterious consequences on the lungs.
... Dor crônica CBD + THC 25 mg à 300mg ao dia (Baron et al., 2018). ...
... It has anti-inflammatory, analgesic, antifungal, antiviral and antioxidant properties, it is able to relax smooth muscles, which makes it a valuable remedy for asthma. 35 Alpha-pinene is responsible for the aroma of fresh pine needles, conifers and sage. Juniper berries are also a source of alpha pinene. ...
In bioelectronic terms, the organism is understood as an integrated circuit of biological piezo, pyroelectrics, ferromagnets and semiconductors, filled with bioplasm and managed electronically by quantum processes. The presence of semiconductors in a biological system is synonymous with the presence of an electronic integrated device, therefore a living organism can be seen as a complex electronic device, analogous to technical devices. Proteins, DNA, RNA, melanin from the biology side, it is a biological structure, from the biochemistry side, they are chemical compounds with different chemical formulas, again from the bioelectronics side it is an electronic material that can serve as structural elements in a bioelectronic device which is an organism. Enzyme transistors were constructed in technical devices from these materials.1
... This synergistic action of terpenes and cannabinoids can improve the benefit of treatment of inflammation, pain, depression, epilepsy, cancer, anxiety (Koltai et al., 2020, Russo, 2011, Baron, 2018. ...
... For instance, previous studies have reported the effects of CBD on pain alleviation and management of oxidative stress and inflammation in endometriosis patients [18,19]. Evidence suggests that CBD has multidirectional properties, including anti-inflammatory, antioxidant [20], immunomodulatory, antiarthritic, neuroprotective, anticonvulsant [21], precognitive [22], antianxiety, antipsychotic, and antiproliferative [22] effects. Accordingly, it has been used to treat hypertension [23,24], neurodegenerative diseases (e.g., multiple sclerosis, Alzheimer's disease, Huntington's disease, and Parkinson's disease), epilepsy [22,25], neuropsychiatric disorders (e.g., anxiety disorders, depression, schizophrenia, and posttraumatic stress disorder after autism spectrum disorders) [22,26], gastrointestinal diseases (e.g., nausea and vomiting, irritable bowel syndrome, and inflammatory bowel disease) [27], rheumatic disease [23], graft versus host disease, and cancer [25,28]. ...
Studies suggest that ovarian hyperstimulation syndrome (OHSS) can be treated by reducing the level of vascular endothelial growth factor (VEGF). However, due to the side effects of commercially available VEGF-reducing drugs, they can be ruled out as a suitable treatment for OHSS; therefore, researchers are looking for new medications to treat OHSS. This study is aimed at investigating the effects of cannabidiol (CBD) in an OHSS model and to evaluate its efficacy in modulating the angiogenesis pathway and VEGF gene expression. For this purpose, 32 female mice were randomly divided into four groups (eight mice per group): control group, group 2 with OHSS induction, group 3 receiving 32 nmol of dimethyl sulfoxide after OHSS induction, and group 4 receiving 30 mg/kg of CBD after OHSS induction. The animals’ body weight, ovarian weight, vascular permeability (VP), and ovarian follicle count were measured, and the levels of VEGF gene and protein expression in the peritoneal fluid were assessed. Based on the results, CBD decreased the body and ovarian weights, VP, and corpus luteum number compared to the OHSS group ( p < 0.05 ). The peritoneal VEGF gene and protein expression levels reduced in the CBD group compared to the OHSS group ( p < 0.05 ). Also, CBD caused OHSS alleviation by suppressing VEGF expression and VP. Overall, CBD downregulated VEGF gene expression and improved VP in OHSS.
... 6 While there are ongoing efforts to synthesize evidence to address gaps in knowledge for the use of medical cannabis for pain, 4 there is an important need for research to help understand the clinical attitudes, barriers, and beliefs regarding the possible implementation of medical cannabis as a pain management option. 7,8 Understanding potential barriers to implementation in clinical practice is a core component in successful knowledge translation efforts, 9 as clinicians are possible drivers of treatment at the individual level. Part of the reason for the inconsistent suggestions from these guidelines regarding dosing, method of administration, and frequency is due to a considerable gap in physicians' knowledge in prescribing medical cannabis. ...
Background:
Medical cannabis is commonly and increasingly used by Canadians to manage chronic pain. As of March 2021, Health Canada reported that approximately 300,000 Canadians who were authorized to access medical cannabis, which is more than a 1000% increase from the 24,000 registered in 2015. Physicians, however, receive limited information on therapeutic cannabis during their training, and their perceptions regarding this therapeutic option are uncertain. This study focused on exploring attitudes and beliefs of pain physicians regarding medical cannabis for the management of chronic noncancer pain.
Methods:
This study utilized a focused ethnography approach. Pain management clinicians within the Greater Toronto and Hamilton Area were recruited through snowball sampling methods, and individually interviewed. We applied thematic analysis to interview transcripts and identified representative quotes. The Hamilton Integrated Research Ethics Board reviewed and approved this project.
Results:
Thirteen physicians who focused their clinical practice on pain management agreed to be interviewed, and three themes regarding medical cannabis emerged: 1) evidence regarding medical cannabis, 2) medical cannabis as first-line therapy for chronic pain, and 3) barriers to accessing medical cannabis. Subthemes of the last theme included out-of-pocket costs, stigma by society and healthcare providers, and lack of knowledge among physicians.
Conclusion:
Despite increasing use of medical cannabis for chronic pain among Canadians, pain physicians in our study expressed concerns regarding the evidence to support this therapy and acknowledged important barriers to access.
Cannabis as a therapeutic agent is increasing in popularity all around the globe, particularly in Western countries, and its potential is now well assessed. On the other hand, each country has its own regulation for the preparation of cannabis macerated oils; in Italy, there are only a few preparation methods allowed. With this work, we aim to perform a stability study of cannabis oils produced with a novel method for the extraction of cannabinoids from cannabis inflorescence. Three different varieties of cannabis were used, with and without the adding of tocopherol acetate as an antioxidant. Cannabinoids were extracted using ethanol at room temperature; then, the solvent was evaporated under reduced pressure and the preparations reconstituted with olive oil. In this work, we assessed the stability of both cannabinoids and terpenes in these formulas over 8 months. Cannabinoid stability was assessed by monitoring the concentrations of THC and CBD, while terpene stability was assessed by monitoring β-Caryophyllene and α-Humulene concentrations. Stability of the extracts was not influenced by the presence of tocopherol acetate, though refrigeration seems to be detrimental for a long storage of products, especially regarding THC concentrations. The improvements offered by this method reside in the flexibility in controlling the concentration of the extract and the ability to produce highly concentrated oils, alongside the possibility to produce standardized oils despite the variability of the starting plant material.
This review article provides an overview of the bioactive compounds of clove, their health benefits, and their potential application in food and beverages. Cloves are rich in phenolic compounds, mainly eugenol, which exhibit antioxidant, anti-inflammatory, antimicrobial, antifungal, and wound-healing properties. Traditional methods of clove extraction, such as Soxhlet and maceration, have limitations. Green extraction methods, such as ultrasound-assisted extraction, pressurised liquid extraction, and microwave-assisted extraction, have shown promising results. The potential application of clove extract in various food and beverage products are also discussed. Finally, future perspectives and challenges for clove extraction are highlighted. Overall, the review highlights the potential of clove extract as a natural source of bioactive compounds for various applications in the food and beverage industry.
Background
During fiscal year 2021–2022, Veterans Affairs Canada (VAC) reimbursed 18,388 veterans for medicinal cannabis at a cost of $153 million. Yet, it is not known whether the reimbursement program is producing a net benefit for veterans.
Aims
This study investigated the views and experiences Canadian that veterans who live with pain have about medicinal cannabis use, including its use for the management of chronic pain, poor sleep, and emotional distress.
Methods
Twelve Canadian veterans who live with pain—eight men, four women; split across four focus groups—were recruited to participate in a semistructured discussion around their experiences with medicinal cannabis use.
Results
Using inductive thematic analysis, seven broad categories were identified: (1) cannabis use behaviors, (2) reasons for cannabis use, (3) outcomes from cannabis use, (4) facilitators of cannabis use, (5) barriers to cannabis use, (6) stigma around cannabis use, and (7) questions and concerns about cannabis use.
Conclusions
Most veterans initiated cannabis use to manage the symptoms of preexisting medical and/or mental health conditions. Despite some negative side effects, most veterans reported improvements in their overall quality of life, sleep, relationships, mood, and pain. Concern remains around the discrepancy between veterans’ qualitative reports of beneficial outcomes from medicinal cannabis use and equivocal findings around the benefit-to-harm ratio in the wider literature. Currently, the VAC reimbursement program remains challenged by unclear indication for which veterans, with what condition(s), at what dose, and in what form medical cannabis is most beneficial.
Temos o prazer de lançar o SEGUNDO livro internacional voltado a área do desenvolvimento do ano de 2023, que tem como título Development and its applications in scientific knowledge , essa obra é editada pela Seven Publicações Ltda, tendo a composição de diversos capítulos voltados ao desenvolvimento e disseminação do conhecimento nas diversas áreas do desenvolvimento.
El cannabis o marihuana es una de las sustancias psicoactivas más consumida en todo el mundo, por lo que conocer la composición y el tipo de cannabis que se comercializa en los entornos urbanos es un insumo necesario para el diseño de políticas en salud pública sustentadas en la evidencia científica. Este estudio caracterizó los principales fitocannabinoides de muestras de marihuana (cigarrillos o cogollos) obtenidas en áreas urbanas y rurales de la ciudad Medellín, en octubre de 2021. Se realizó un muestreo no probabilístico a conveniencia en el que se recolectaron 87 muestras de marihuana donadas por consumidores en diferentes puntos de recolección en toda la ciudad, aplicando las técnicas de cromatografía de gases masas e ionización de llama para la caracterización de los fitocanabinoides. Se encontró el tetrahidrocannabinol como el constituyente principal de la marihuana circulante en Medellín, donde el 67,8% de las muestras presentaba un rango toxicológico alto o superior para THC; lo anterior en un contexto donde el mercado desregulado limita la posibilidad que tienen los consumidores en la práctica de calibrar o decidir la concentración de cannabinoides en sus dosis.
Cannabis sativa, popularly known as “marijuana,” poses a problem since it may have both beneficial and harmful effects. Cannabis has long been used for medicinal and recreational purposes, which demonstrates its value as a plant. Instead of this, enough evidence suggests that abusing this wonder herb can have negative effects on a number of organs and organ systems, such as the pulmonary system, the body's defense system, the cardiovascular system, etc. Additionally, it may affect both male and female potency and may also have clastogenic effects. Yet, it cannot be ruled out that there are some benefits to using marijuana responsibly, since it has been shown to be a miraculous treatment for atrophy, acute pain, a loss of muscular tone, motion sickness, and insomnia. This chapter will attempt to provide a thorough understanding of the various health effects of the herb and its extracted active bioactive ingredients.
More than 200 million tons of plant oils and animal fats are produced annually worldwide from oil, crops, and the rendered animal fat industry. Triacylglycerol, an abundant energy-dense compound, is the major form of lipid in oils and fats. While oils or fats are very important raw materials and functional ingredients for food or related products, a significant portion is currently diverted to or recovered as waste. To significantly increase the value of waste oils or fats and expand their applications with a minimal environmental footprint, microbial biomanufacturing is presented as an effective strategy for adding value. Though both bacteria and yeast can be engineered to use oils or fats as the biomanufacturing feedstocks, the yeast Yarrowia lipolytica is presented as one of the most attractive platforms. Y. lipolytica is oleaginous, generally regarded as safe, demonstrated as a promising industrial producer, and has unique capabilities for efficient catabolism and bioconversion of lipid substrates. This review summarizes the major challenges and opportunities for Y. lipolytica as a new biomanufacturing platform for the production of value-added products from oils and fats. This review also discusses relevant cellular and metabolic engineering strategies such as fatty acid transport, fatty acid catabolism and bioconversion, redox balances and energy yield, cell morphology and stress response, and bioreaction engineering. Finally, a review of specific product classes including long-chain diacids, wax esters, terpenes, and carotenoids with unique synthesis opportunities from oils and fats highlights the potential of Y. lipolytica.
Hemp press cake flour (HPCF) is a by-product of hemp oil production rich in proteins, carbohydrates, minerals, vitamins, oleochemicals, and phytochemicals. The purpose of this study was to investigate how the addition of HPCF to bovine and ovine plain yoghurts at concentrations of 0%, 2%, 4%, 6%, 8%, and 10% could change the physicochemical, microbiological, and sensory properties of the yoghurts, focusing on the improvement of quality and antioxidant activity, and the issue of food by-products and their utilisation. The results showed that the addition of HPCF to yoghurts significantly affected their properties, including an increase in pH and decrease in titratable acidity, change in colour to darker, reddish or yellowish hue, and a rise in total polyphenols and antioxidant activity during storage. Yoghurts fortified with 4% and 6% HPCF exhibited the best sensory properties, thus maintaining viable starter counts in the yoghurts during the study period. There were no statistically significant differences between the control yoghurts and the samples with 4% added HPCF in terms of overall sensory score while maintaining viable starter counts during the seven-day storage. These results suggest that the addition of HPCF to yoghurts can improve product quality and create functional products and may have potential in sustainable food waste management.
O I Congresso Nacional de Ciências Médicas e da Saúde On-line (I CONACIMES), organizado pela Bio10 Digital Cursos, com o apoio científico da revista Journal of Education, Science and Health - JESH e do Dr. Willy França, ocorreu no período de 13 a 16 de outubro de 2021, com carga horária de 40 horas, incluindo palestras, minicursos, apresentação de trabalhos e menção honrosa. O CONACIMES contou com a participação de graduandos, pós-graduandos, profissionais e pesquisadores da área de saúde, dos diversos cantos do Brasil e das mais variadas Instituições de Ensino e Pesquisa do país. O evento recebeu submissões, no formato de resumos simples e expandidos. Durante a programação ocorreu exposição em e-pôster e apresentação oral, momento de debate agradável e de troca de conhecimentos que enriqueceu a experiência dos autores. Os três melhores trabalhos em cada modalidade de apresentação receberam menção honrosa. O objetivo dessa ação é incentivar a pesquisa, principalmente por autores iniciantes e estimular a produção acadêmica de graduandos, graduados e profissionais da área. Queremos agradecer a todos os envolvidos no CONACIMES: palestrantes, avaliadores, divulgadores, participantes, monitores e todos os membros da Comissão Organizadora que possibilitaram que esse evento ocorresse. Saibam que sem vocês não seria possível a realização do CONACIMES 2021. Esperamos continuar com outras edições e crescendo cada vez mais. Nosso muito obrigado.
Kenevir ilaç ve sanayi
Complementary therapies are commonly sought for treatment of pediatric headache by primary care physicians, specialists, and parents alike. Herein, we describe the use of nutraceuticals, manual therapies, and acupuncture for headache treatment. We specifically address safety and efficacy evidence when available for children and teens.
We attempted to identify the antinociceptive and anti-inflammatory actions of the monoterpene p-cymene. Firstly, behavioural screening was carried out to verify the influence of p-cymene [25, 50, and 100 mg/kg intraperitoneal (i.p.)] on the central nervous system (CNS) activity. The antinociceptive activity of p-cymene was evaluated by the acetic acidinduced writhing response, formalin, and hot-plate test, respectively. The leukocyte migration induced by injection of carrageenan was used to assess the anti-inflammatory activity. p-Cymene showed depressant activity on CNS after 4 h of treatment and also a possible action on the autonomous nervous system (ANS), mainly at the dose of 100 mg/kg (i.p.). It was found that p-cymene (50 and 100 mg/kg, i.p.) significantly (p < 0.05) reduced the writhing responses induced by acetic acid. p-Cymene also decreased the licking time in the first and second phase, respectively, of the formalin test. The results of the hot-plate test showed that all doses of p-cymene increased significantly the latency time of the response to the thermal stimulus in both licking and jumping parameters. In addition, there was a significantly (p < 0.05) decreased leukocyte migration at all doses of p-cymene. The experimental data demonstrate that p-cymene possesses antinociceptive and anti-inflammatory activities
Background
Medicinal cannabis registries typically report pain as the most common reason for use. It would be clinically useful to identify patterns of cannabis treatment in migraine and headache, as compared to arthritis and chronic pain, and to analyze preferred cannabis strains, biochemical profiles, and prescription medication substitutions with cannabis.
Methods
Via electronic survey in medicinal cannabis patients with headache, arthritis, and chronic pain, demographics and patterns of cannabis use including methods, frequency, quantity, preferred strains, cannabinoid and terpene profiles, and prescription substitutions were recorded. Cannabis use for migraine among headache patients was assessed via the ID Migraine™ questionnaire, a validated screen used to predict the probability of migraine.
Results
Of 2032 patients, 21 illnesses were treated with cannabis. Pain syndromes accounted for 42.4% (n = 861) overall; chronic pain 29.4% (n = 598;), arthritis 9.3% (n = 188), and headache 3.7% (n = 75;). Across all 21 illnesses, headache was a symptom treated with cannabis in 24.9% (n = 505). These patients were given the ID Migraine™ questionnaire, with 68% (n = 343) giving 3 “Yes” responses, 20% (n = 102) giving 2 “Yes” responses (97% and 93% probability of migraine, respectively). Therefore, 88% (n = 445) of headache patients were treating probable migraine with cannabis. Hybrid strains were most preferred across all pain subtypes, with “OG Shark” the most preferred strain in the ID Migraine™ and headache groups. Many pain patients substituted prescription medications with cannabis (41.2–59.5%), most commonly opiates/opioids (40.5–72.8%). Prescription substitution in headache patients included opiates/opioids (43.4%), anti-depressant/anti-anxiety (39%), NSAIDs (21%), triptans (8.1%), anti-convulsants (7.7%), muscle relaxers (7%), ergots (0.4%).
Conclusions
Chronic pain was the most common reason for cannabis use, consistent with most registries. The majority of headache patients treating with cannabis were positive for migraine. Hybrid strains were preferred in ID Migraine™, headache, and most pain groups, with “OG Shark”, a high THC (Δ9-tetrahydrocannabinol)/THCA (tetrahydrocannabinolic acid), low CBD (cannabidiol)/CBDA (cannabidiolic acid), strain with predominant terpenes β-caryophyllene and β-myrcene, most preferred in the headache and ID Migraine™ groups. This could reflect the potent analgesic, anti-inflammatory, and anti-emetic properties of THC, with anti-inflammatory and analgesic properties of β-caryophyllene and β-myrcene. Opiates/opioids were most commonly substituted with cannabis. Prospective studies are needed, but results may provide early insight into optimizing crossbred cannabis strains, synergistic biochemical profiles, dosing, and patterns of use in the treatment of headache, migraine, and chronic pain syndromes.
9-Tetrahydrocannabinol (THC) has complex effects on the cardiovascular system. We aimed to systematically review studies of THC and haemodynamic alterations. PubMed, Medline, and EMBASE were searched for relevant studies. Changes in blood pressure (BP), heart rate (HR), and blood flow (BF) were analysed using the Cochrane Review Manager Software. Thirty-one studies met the eligibility criteria. Fourteen publications assessed BP (number, n = 541), 22 HR (n = 567), and 3 BF (n = 45). Acute THC dosing reduced BP and HR in anaesthetised animals (BP, mean difference (MD) −19.7 mmHg, p < 0.00001; HR, MD −53.49 bpm, p < 0.00001), conscious animals (BP, MD −12.3 mmHg, p = 0.0007; HR, MD −30.05 bpm, p < 0.00001), and animal models of stress or hypertension (BP, MD −61.37 mmHg, p = 0.03) and increased cerebral BF in murine stroke models (MD 32.35%, p < 0.00001). Chronic dosing increased BF in large arteries in anaesthetised animals (MD 21.95 mL/min, p = 0.05) and reduced BP in models of stress or hypertension (MD −22.09 mmHg, p < 0.00001). In humans, acute administration increased HR (MD 8.16 bpm, p < 0.00001). THC acts differently according to species and experimental conditions, causing bradycardia, hypotension and increased BF in animals; and causing increased HR in humans. Data is limited, and further studies assessing THC-induced haemodynamic changes in humans should be considered.
Summary
Background
Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level.
Methods
We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development.
Findings
Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs.
Interpretation
Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services.
Funding
Bill & Melinda Gates Foundation.
Background
North America is currently in the grips of a crisis rooted in the use of licit and illicit opioid-based analgesics. Drug overdose is the leading cause of accidental death in Canada and the US, and the growing toll of opioid-related morbidity and mortality requires a diversity of novel therapeutic and harm reduction-based interventions. Research suggests that increasing adult access to both medical and recreational cannabis has significant positive impacts on public health and safety as a result of substitution effect. Observational and epidemiological studies have found that medical cannabis programs are associated with a reduction in the use of opioids and associated morbidity and mortality. Aims and Methods
This paper presents an evidence-based rationale for cannabis-based interventions in the opioid overdose crisis informed by research on substitution effect, proposing three important windows of opportunity for cannabis for therapeutic purposes (CTP) to play a role in reducing opioid use and interrupting the cycle towards opioid use disorder: 1) prior to opioid introduction in the treatment of chronic pain; 2) as an opioid reduction strategy for those patients already using opioids; and 3) as an adjunct therapy to methadone or suboxone treatment in order to increase treatment success rates. The commentary explores potential obstacles and limitations to these proposed interventions, and as well as strategies to monitor their impact on public health and safety. Conclusion
The growing body of research supporting the medical use of cannabis as an adjunct or substitute for opioids creates an evidence-based rationale for governments, health care providers, and academic researchers to consider the implementation and assessment of cannabis-based interventions in the opioid crisis.
Beneficial effects of cannabidiol (CBD) have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood. Similar to clinical antidepressant or atypical antipsychotic drugs, recent findings clearly indicate that CBD, either acutely or repeatedly administered, induces plastic changes. For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia. More recently, it was found that CBD modulates cell fate regulatory pathways such as autophagy and others critical pathways for neuronal survival in neurodegenerative experimental models, suggesting the potential benefit of CBD treatment for psychiatric/cognitive symptoms associated with neurodegeneration. These changes and their possible association with CBD beneficial effects in psychiatric disorders are reviewed here.
Various genetic factors can predispose individuals to migraines. For example, studies have shown that a decrease in expression of the cnr1 gene, which encodes the cannabinoid receptor type 1 (CB1) receptor, is associated with migraine and trigeminovascular activation.⁷⁰ Women who experience migraine also have increased activities of fatty acid amide hydrolase (FAAH), an enzyme used to degrade the endocannabinoid anandamide (AEA), and the endocannabinoid membrane transporter (EMT), a membrane transporter for AEA, leading to an overall decrease in levels of endocannabinoids.⁷³ This finding could partially explain the increased prevalence of migraines in women. An examination of cerebrospinal fluid shows that individuals who experience migraines have decreased levels of AEA and increased levels of CGRP and NO (normally inhibited by AEA). These findings support the proposed theory that alterations in endocannabinoid function with reductions in endocannabinoids such as AEA may be one of the mechanisms underlying migraine. A feature of headache disorders is that they are highly associated with other comorbidities, including anxiety and mood disorders, allergies, chronic pain disorders, and epilepsy.⁸⁶ The endocannabinoid deficiency hypothesis provides a possible mechanism underlying not only migraine but also diseases such as fibromyalgia and irritable bowel syndrome.⁷² Although the endocannabinoid deficiency hypothesis is still speculative and in need of further study, it suggests that exogenous stimulators of the endocannabinoid system, such as cannabis, could treat these diseases at their source.⁸⁷
Despite cannabidiol (CBD) having numerous cardiovascular effects in vitro, its haemodynamic effects in vivo are unclear. Nonetheless, the clinical use of CBD (Epidiolex) is becoming more widespread. The aim of this systematic review was to establish whether CBD is associated with changes in haemodynamics in vivo. Twenty-five studies that assessed the haemodynamic effects of CBD (from PubMed, Medline and EMBASE) were systematically reviewed and meta-analyzed. Data on blood pressure (BP), heart rate (HR), and blood flow (BF) were extracted and analyzed using random effects models. Twenty-two publications assessed BP and HR among 6 species (BP n = 344 and HR n = 395), and 5 publications assessed BF in 3 species (n = 56) after acute dosing of CBD. Chronic dosing was assessed in 4 publications in 3 species (total subjects BP, n = 6; HR, n = 27; BF, n = 3). Acute CBD dosing had no effect on BP or HR under control conditions. Similarly, chronic dosing with CBD had no effect on HR. In models of stress, acute CBD administration significantly reduced the increase in BP and HR induced by stress (BP, mean difference (MD) −3.54, 95% CI −5.19, −1.9, p < 0.0001; HR, MD −16.23, 95% CI −26.44, −6.02, p = 0.002). In mouse models of stroke, CBD significantly increased cerebral blood flow (CBF, standardized mean difference (SMD) 1.62, 95% CI 0.41, 2.83, p = 0.009). Heterogeneity among the studies was present, there was no publication bias except in HR of control and stressful conditions after acute CBD dosing, and median study quality was 5 out of 9 (ranging from 1 to 8). From the limited data available, we conclude that acute and chronic administration of CBD had no effect on BP or HR under control conditions, but reduces BP and HR in stressful conditions, and increases cerebral blood flow (CBF) in mouse models of stroke. Further studies are required to fully understand the potential haemodynamic effects of CBD in humans under normal and pathological conditions.
The endocannabinoid system plays a regulatory role in a number of physiological processes and has been found altered in different pathological conditions, including movement disorders. The interactions between cannabinoids and dopamine in the basal ganglia are remarkably complex and involve both the modulation of other neurotransmitters (γ-aminobutyric acid, glutamate, opioids, peptides) and the activation of different receptors subtypes (cannabinoid receptor type 1 and 2). In the last years, experimental studies contributed to enrich this scenario reporting interactions between cannabinoids and other receptor systems (transient receptor potential vanilloid type 1 cation channel, adenosine receptors, 5-hydroxytryptamine receptors). The improved knowledge, adding new interpretation on the biochemical interaction between cannabinoids and other signaling pathways, may contribute to develop new pharmacological strategies. A number of preclinical studies in different experimental Parkinson's disease (PD) models demonstrated that modulating the cannabinoid system may be useful to treat some motor symptoms. Despite new cannabinoid-based medicines have been proposed for motor and nonmotor symptoms of PD, so far, results from clinical studies are controversial and inconclusive. Further clinical studies involving larger samples of patients, appropriate molecular targets, and specific clinical outcome measures are needed to clarify the effectiveness of cannabinoid-based therapies.
Alzheimer's disease (AD) is a debilitating neurodegenerative disease that is affecting an increasing number of people. It is characterized by the accumulation of amyloid-β and tau hyperphosphorylation as well as neuroinflammation and oxidative stress. Current AD treatments do not stop or reverse the disease progression, highlighting the need for new, more effective therapeutics. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has demonstrated neuroprotective, anti-inflammatory and antioxidant properties in vitro. Thus, it is investigated as a potential multifunctional treatment option for AD. Here, we summarize the current status quo of in vivo effects of CBD in established pharmacological and transgenic animal models for AD. The studies demonstrate the ability of CBD to reduce reactive gliosis and the neuroinflammatory response as well as to promote neurogenesis. Importantly, CBD also reverses and prevents the development of cognitive deficits in AD rodent models. Interestingly, combination therapies of CBD and Δ9-tetrahydrocannabinol (THC), the main active ingredient of cannabis sativa, show that CBD can antagonize the psychoactive effects associated with THC and possibly mediate greater therapeutic benefits than either phytocannabinoid alone. The studies provide “proof of principle” that CBD and possibly CBD-THC combinations are valid candidates for novel AD therapies. Further investigations should address the long-term potential of CBD and evaluate mechanisms involved in the therapeutic effects described.
Ethopharmacologic relevance:
Juniperus communis. L. is a shrub or small evergreen tree, native to Europe, South Asia, and North America, and belongs to family Cupressaceae. It has been used traditionally in unani system and in Swedish medicine as a decoction in inflammatory diseases. The main chemical constituents, which were reported in J. communis L. was α-pinene,, apigenin, sabinene, β-sitosterol, campesterol, limonene, Amentoflavone (AF), cupressuflavone, and many others.
Aim:
The aim of present study was to isolate the amentoflavone from the plant juniperus communis L. extracts and its protective effects against Freund's adjuvant induced arthritis in rats.
Material methods:
Adjuvant arthritis was induced by an injection of 1mg heat killed Mycobacterium tuberculosis (CFA) into the left hind paw of rat by sub planter route (at day 0). The experiment was designed and modified as per method available in literature.
Results:
The study showed that at a dose of 40mg/kg of amentoflavone (AF) from methanolic extract of Juniperus Communis L. possessed potentially useful anti-arthritic activity as it gave a positive result in controlling inflammation in the adjuvant induced experimental model.
Conclusion:
From the present experimental findings of both pharmacological and biochemical parameters observed, it had been concluded that at the doses of 20mg/kg and 40mg/kg of AF fraction from methanolic extract of Juniperus communis L. It possesses useful anti-arthritic activity since it gives a positive result in controlling inflammation in the adjuvant induced arthritic model in rats. The drug is a promising anti-arthritic agent of plant origin in the treatment of inflammatory disorders.
There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9-THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.
This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing canna- binoids in pain treatment. Tetrahydrocannabinol (THC, Marinol ® ) and nabilone (Cesamet ® ) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex ® , a cannabis derived oromucosal spray containing equal proportions of THC (partial CB 1 receptor agonist ) and can- nabidiol (CBD, a non-euphoriant, anti-infl ammatory analgesic with CB 1 receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numer- ous randomized clinical trials have demonstrated safety and effi cacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profi les. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise.
Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for “CBD botanical drug substance,” on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage – after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.
Objective:
Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties. The authors assessed the safety and effectiveness of CBD in patients with schizophrenia.
Method:
In an exploratory double-blind parallel-group trial, patients with schizophrenia were randomized in a 1:1 ratio to receive CBD (1000 mg/day; N=43) or placebo (N=45) alongside their existing antipsychotic medication. Participants were assessed before and after treatment using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), the Global Assessment of Functioning scale (GAF), and the improvement and severity scales of the Clinical Global Impressions Scale (CGI-I and CGI-S).
Results:
After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms (PANSS: treatment difference=-1.4, 95% CI=-2.5, -0.2) and were more likely to have been rated as improved (CGI-I: treatment difference=-0.5, 95% CI=-0.8, -0.1) and as not severely unwell (CGI-S: treatment difference=-0.3, 95% CI=-0.5, 0.0) by the treating clinician. Patients who received CBD also showed greater improvements that fell short of statistical significance in cognitive performance (BACS: treatment difference=1.31, 95% CI=-0.10, 2.72) and in overall functioning (GAF: treatment difference=3.0, 95% CI=-0.4, 6.4). CBD was well tolerated, and rates of adverse events were similar between the CBD and placebo groups.
Conclusions:
These findings suggest that CBD has beneficial effects in patients with schizophrenia. As CBD's effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.
A major factor associated with poor prognostic outcome after a first psychotic break is cannabis misuse, which is prevalent in schizophrenia and particularly common in individuals with recent-onset psychosis. Behavioral interventions aimed at reducing cannabis use have been unsuccessful in this population. Cannabidiol (CBD) is a phytocannabinoid found in cannabis, although at low concentrations in modern-day strains. CBD has a broad pharmacological profile, but contrary to ∆9-tetrahydrocannabinol (THC), CBD does not activate CB1 or CB2 receptors and has at most subtle subjective effects. Growing evidence indicates that CBD acts as an antipsychotic and anxiolytic, and several reports suggest neuroprotective effects. Moreover, CBD attenuates THC's detrimental effects, both acutely and chronically, including psychotogenic, anxiogenic, and deleterious cognitive effects. This suggests that CBD may improve the disease trajectory of individuals with early psychosis and comorbid cannabis misuse in particular-a population with currently poor prognostic outcome and no specialized effective intervention.
Objectives:
To examine the association between Colorado's legalization of recreational cannabis use and opioid-related deaths.
Methods:
We used an interrupted time-series design (2000-2015) to compare changes in level and slope of monthly opioid-related deaths before and after Colorado stores began selling recreational cannabis. We also describe the percent change in opioid-related deaths by comparing the unadjusted model-smoothed number of deaths at the end of follow-up with the number of deaths just prior to legalization.
Results:
Colorado's legalization of recreational cannabis sales and use resulted in a 0.7 deaths per month (b = -0.68; 95% confidence interval = -1.34, -0.03) reduction in opioid-related deaths. This reduction represents a reversal of the upward trend in opioid-related deaths in Colorado.
Conclusions:
Legalization of cannabis in Colorado was associated with short-term reductions in opioid-related deaths. As additional data become available, research should replicate these analyses in other states with legal recreational cannabis.
Objective:
We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants.
Design:
Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex. Inflammatory cytokine secretion was determined using ELISA. Receptor mechanisms were investigated using antagonists for CB1, CB2, PPARα, PPARγ, TRPV1 and GPR55.
Results:
IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants. Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants. CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2 antagonist AM630 and TRPV1 antagonist SB366791. PEA effects were blocked by the PPARα antagonist GW6471. PEA and CBD were anti-inflammatory in IBD and appendicitis explants.
Conclusion:
PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy.
Pain is the most common manifestation of both acute and chronic inflammation that often challenges patients with rheumatic disease. Simply, we attribute this to local joint changes of pH in joints, the formation of radicals, enhanced joint pressure, or cytokine release acting on local nerves to produce pain. However, there is a more complex interplay of interactions between cytokines, mediators of inflammation, and ion channels that influence the final immune response and our perception of pain. Endocannabinoids, a group of less well-known endogenous bioactive lipids, have such manifold immunomodulatory effects able to influence both inflammation and pain. In this review, we overview the endocannabinoid system, its role in pain, inflammation, and immune regulation, and highlight the emerging challenges and therapeutic hopes.
The essential oil of black cumin seeds, Nigella sativa L., was tested for a possible antioxidant activity. A rapid evaluation for antioxidants, using two TLC screening methods, showed that thymoquinone and the components carvacrol, t-anethole and 4-terpineol demonstrated respectable radical scavenging property. These four constituents and the essential oil possessed variable antioxidant activity when tested in the diphenylpicrylhydracyl assay for non-specific hydrogen atom or electron donating activity. They were also effective ·OH radical scavenging agents in the assay for non-enzymatic lipid peroxidation in liposomes and the deoxyribose degradation assay.
Introduction: Epilepsy is one of the world’s oldest recognized and prevalent neurological diseases. It has a great negative impact on patients’ quality of life (QOL) as a consequence of treatment resistant seizures in about 30% of patients together with drugs’ side effects and comorbidities. Therefore, new drugs are needed and cannabinoids, above all cannabidiol, have recently gathered attention.
Areas Covered: This review summarizes the scientific data from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including drugs acting on the endocannabinoid system.
Expert commentary: Despite the fact that cannabis has been used for many purposes over 4 millennia, the development of drugs based on cannabinoids has been very slow. Only recently, research has focused on their potential effects and CBD is the first treatment of this group with clinical evidence of efficacy in children with Dravet syndrome; moreover, other studies are currently ongoing to confirm its effectiveness in patients with epilepsy. On the other hand, it will be of interest to understand whether drugs acting on the endocannabinoid system will be able to reach the market and prove their known preclinical efficacy also in patients with epilepsy.
A series of novel α-terpineol derivatives were designed and synthesized through structural derivatization of the tertiary hydroxyl moiety or reduction of the double bond. Of the resulting compounds, eight compounds enhanced relaxation of airway smooth muscle (ASM) compared to the α-terpineol precursor, and four compounds (4a, 4d, 4e, and 4i)were superior or comparable to aminophylline at a concentration of 0.75 mmol/L. Assays for 3′-5′-Cyclic adenosine monophpsphate (cAMP) activation revealed that some representative α-terpineol derivatives in this series were capable of upregulating the level of cAMP in ASM cells. Further in vivo investigation using the asthmatic rat model, illustrated that treatment with the compounds 4a and 4e resulted in significantly lowered lung resistance (RL) and enhanced dynamic lung compliance (Cldyn), two important parameters for lung fuction. Moreover, treatment with 4e downregulated the levels of both IL-4 and IL-17. Due to its several favorable physiological functions, including ASM relaxation activity, cAMP activation capability, and in vivo anti-asthmatic efficacy, 4e is a promising remedy for bronchial asthma, meriting extensive development.
Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive impairment, and a narrow therapeutic window, making the search for novel analgesics ever more important. In this article, we review the role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain. Herein, we briefly cover the discovery of the EC system and its role in pain processing pathways, before concentrating on three areas of current major interest in EC pain research; 1. Pharmacological enhancement of endocannabinoid activity (via blockade of EC metabolism or allosteric modulation of CB1receptors); 2. The EC System and stress-induced modulation of pain; and 3. The EC system & medial prefrontal cortex (mPFC) dysfunction in pain states. Whilst we focus predominantly on the preclinical data, we also include extensive discussion of recent clinical failures of endocannabinoid-related therapies, the future potential of these approaches, and important directions for future research on the EC system and pain.
Background:
Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid used in multiple sclerosis and intractable epilepsies. Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. The aim of this study was to investigate if CBD reduces BP in humans.
Methods:
Nine healthy male volunteers were given 600 mg of CBD or placebo in a randomized, placebo-controlled, double-blind, crossover study. Cardiovascular parameters were monitored using a finometer and laser Doppler.
Results:
CBD reduced resting systolic BP (-6 mmHg; P < 0.05) and stroke volume (-8 ml; P < 0.05), with increased heart rate (HR) and maintained cardiac output. Subjects who had taken CBD had lower BP (-5 mmHg; P < 0.05, especially before and after stress), increased HR (+10 bpm; P < 0.01), decreased stroke volume (-13 ml; P < 0.01), and a blunted forearm skin blood flow response to isometric exercise. In response to cold stress, subjects who had taken CBD had blunted BP (-6 mmHg; P < 0.01) and increased HR (+7 bpm; P < 0.05), with lower total peripheral resistance.
Conclusions:
This data shows that acute administration of CBD reduces resting BP and the BP increase to stress in humans, associated with increased HR. These hemodynamic changes should be considered for people taking CBD. Further research is required to establish whether CBD has a role in the treatment of cardiovascular disorders.
The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment. Accordingly, cannabinoid compounds have been reported to inhibit tumor growth and spreading in numerous rodent models. The underlying mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor cells as well as inhibition of tumor cell invasion and angiogenic features of endothelial cells. In addition, cannabinoids have been shown to suppress epithelial-to-mesenchymal transition, to enhance tumor immune surveillance, and to support chemotherapeutics’ effects on drug-resistant cancer cells. However, unwanted side effects include psychoactivity and possibly pathogenic effects on liver health. Other cannabinoids such as the nonpsychoactive cannabidiol exert a comparatively good safety profile while exhibiting considerable anticancer properties. So far experience with anticarcinogenic effects of cannabinoids is confined to in vitro studies and animal models. Although a bench-to-bedside conversion remains to be established, the current knowledge suggests cannabinoid compounds to serve as a group of drugs that may offer significant advantages for patients suffering from cancer diseases. The present review summarizes the role of the endocannabinoid system and cannabinoid compounds in tumor progression.
Phytocannabinoids possess anticancer activity when used alone, and a number have also been shown to combine favourably with each other in vitro in leukaemia cells to generate improved activity. We have investigated the effect of pairing cannabinoids and assessed their anticancer activity in cell line models. Those most effective were then used with the common anti-leukaemia drugs cytarabine and vincristine, and the effects of this combination therapy on cell death studied in vitro. Results show a number of cannabinoids could be paired together to generate an effect superior to that achieved if the components were used individually. For example, in HL60 cells, the IC50 values at 48 h for cannabidiol (CBD) and tetrahydrocannabinol (THC) when used alone were 8 and 13 µM, respectively; however, if used together, it was 4 µM. Median-effect analysis confirmed the benefit of using cannabinoids in pairs, with calculated combination indices being <1 in a number of cases. The most efficacious cannabinoid-pairs subsequently synergised further when combined with the chemotherapy agents, and were also able to sensitise leukaemia cells to their cytotoxic effects. The sequence of administration of these drugs was important though; using cannabinoids after chemotherapy resulted in greater induction of apoptosis, whilst this was the opposite when the schedule of administration was reversed. Our results suggest that when certain cannabinoids are paired together, the resulting product can be combined synergistically with common anti-leukaemia drugs allowing the dose of the cytotoxic agents to be dramatically reduced yet still remain efficacious. Nevertheless, the sequence of drug administration is crucial to the success of these triple combinations and should be considered when planning such treatments.
Background
The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome.
Methods
In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period.
Results
The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, −22.8 percentage points; 95% confidence interval [CI], −41.1 to −5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient’s overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group.
Conclusions
Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375.)
The endocannabinoid (eCB) system has attracted attention for its role in various behavioral and brain functions, and as a therapeutic target in neuropsychiatric disease states, including anxiety disorders and other conditions resulting from dysfunctional responses to stress. In this mini-review, we highlight components of the eCB system that offer potential ‘druggable’ targets for new anxiolytic medications, emphasizing some of the less well-discussed options. We discuss how selectively amplifying eCBs recruitment by interfering with eCB-degradation, via fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), has been linked to reductions in anxiety-like behaviors in rodents and variation in human anxiety symptoms. We also discuss a non-canonical route to regulate eCB degradation that involves interfering with cyclooxygenase-2 (COX-2). Next, we discuss approaches to targeting eCB receptor-signaling in ways that do not involve the cannabinoid receptor subtype 1 (CB1R); by targeting the CB2R subtype and the transient receptor potential vanilloid type 1 (TRPV1). Finally, we review evidence that cannabidiol (CBD), while representing a less specific pharmacological approach, may be another way to modulate eCBs and interacting neurotransmitter systems to alleviate anxiety. Taken together, these various approaches provide a range of plausible paths to developing novel compounds that could prove useful for treating trauma-related and anxiety disorders.
Limonene, linalool and citral are common non-phenolic terpenoid components of essential oils, with attributed controversial antioxidant properties. The kinetics of their antioxidant activity was investigated using the inhibited autoxidation of a standard model substrate. Results indicate that antioxidant behavior of limonene, linalool and citral occurs by co-oxidation with the substrate, due to very fast self-termination and cross-termination of the oxidative chain. Rate constants kp and 2kt, (M⁻¹s⁻¹) at 30 °C were 4.5 and 3.5 × 10⁶ for limonene, 2.2 and 9.0 × 10⁵ for linalool and 39 and 1.0 × 10⁸ for citral. Behavior is bimodal antioxidant/pro-oxidant depending on the concentration. Calculations at the M05/6-311+g(2df,2p) level indicate that citral reacts selectively at the aldehyde C-H having activation enthalpy and energy respectively lower by 1.3 and 1.8 kcal/mol compared to the most activated allyl position. Their termination-enhancing antioxidant chemistry might be relevant in food preservation and could be exploited under appropriate settings.
Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie an opioid-sparing effect). The aim of this study was to conduct a systematic review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED50) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% CI 1.95, 6.76; n=6) than the ED50 of morphine alone. In addition, the ED50 for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED50 of codeine alone. One case series (n=3) provided very low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, while one of the nine clinical studies identified provided very low-quality evidence of such an effect. Prospective high-quality controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.
Over the past years, several lines of evidence support a therapeutic potential of Cannabis derivatives and in particular phytocannabinoids. Δ(9)-THC and cannabidiol (CBD) are the most abundant phytocannabinoids in Cannabis plants and therapeutic application for both compounds have been suggested. However, CBD is recently emerging as a therapeutic agent in numerous pathological conditions since devoid of the psychoactive side effects exhibited instead by Δ(9)-THC. In this review, we highlight the pharmacological activities of CBD, its cannabinoid receptor-dependent and -independent action, its biological effects focusing on immunomodulation, angiogenetic properties, and modulation of neuronal and cardiovascular function. Furthermore, the therapeutic potential of cannabidiol is also highlighted, in particular in nuerological diseases and cancer.